When cells are exposed to stress such as high temperature, high osmotic pressure, metabolic inhibition, presence of heavy metal, and viral infection, a family of proteins called "heat shock proteins" (hereinafter referred to as "HSP") are induced and synthesized in a short period of time to cause a defense reaction against the stress. HSP presents broad homology ranging from procaryotic cells to eucaryotic cells, and it is roughly divided into several groups (HSP 60 group, HSP 70 group, HSP 90 group, TRiC group, and miscellaneous group) (Hendrick, J. P. and Hartl, F. V., Annu. Rev. Biochem., 62, 349-384 (1993)).
The mechanism of stress resistance exhibited by HSP resides in the function of HSP to form higher-order structures of proteins (folding of proteins). Namely, when a protein is denatured due to stress, and becomes incapable of forming a correct higher-order structure, HSP binds to the protein, and the protein is subjected to refolding into the correct higher-order structure. Thus the protein can be returned to have its normal function.
HSP, which functions for the formation of higher-order structures of proteins as described above, has been revealed to serve as a molecular chaperon not only for denatured proteins but also for cells in a normal state through the process of protein folding, assembly, membrane transport and so on. Accordingly, its importance is recognized and widely noticed (Ellis, R. J. et al., Science, 250, 954-959 (1990)). The term "chaperon" means a supporter. This designation results from the fact that HSP binds to various proteins, and it exhibits its function.
Expression of HSP is induced when cells are exposed to stress as described above. The induction is usually temporary. It attenuates soon, and a new steady state is achieved. It has been revealed that the induction of HSP, is made at the transcription level (Cowing, D. C. et al., Proc. Natl. Acad. Sci. USA, 80, 2679-2683 (1985); Zhou, Y. N. et al., J. Bacteriol., 170, 3640-3649 (1988)). It is known that each of the family of HSP genes has a promoter structure called "heat shock promoter", and sigma-32 (.sigma..sup.=) is present which is a .sigma. (sigma) factor to specifically function for the heat shock promoter. It is known that .sigma..sup.= is a protein encoded by a rpoH gene, having an extremely short half-life of about 1 minute, and it closely relates to the temporary induction of HSP (Straus, D. B. et al., Nature, 329, 348-351 (1987)). It has been revealed that expression control for .sigma..sup.= itself is made at the transcription level and at the translation level, however, major control is made at the translation level.
The induction of HSP by heat shock is caused by two mechanisms of increase in synthetic amount of .sigma..sup.= and stabilization thereof. Among them, as for the increase in synthetic amount of .sigma..sup.=, it has been already revealed that the structure of .sigma..sup.= changes due to heat, and thus translation is accelerated (Yura, T. et al., Annu. Rev. Microbiol., 47, 321-350 (1993)). As for the stabilization of .sigma..sup.=, it has been shown that HSP (DnaK or the like) participates in degradation of .sigma..sup.=, assuming that feedback control by HSP functions (Tilly, K. et al., Cell, 34, 641-646 (1983); Liberek, K., Proc. Natl. Acad. Sci. USA, 89, 3516-3520 (1994)).
As for Escherichia coli (E. coli), it is known that the growth of cells relates to HSP in the presence of stress as described above (Meury, J. et al., FEMS Microbiol. Lett., 113, 93-100 (1993)). It is also known that production of human growth hormone is affected by dnaK, and secretion of procollagenase is affected by groE (Hockney, R. C., Trends in Biotechnology, 12, 456 (1994)). However, no relationship is known between HSP and productivity of fermentative products such as amino acids and nucleic acids and the like. As for coryneform bacteria, no relationship is known between HSP and growth, and no relationship is also known between HSP and productivity of fermentative products.